hormone therapy and ogx-011 before radical prostatectomy in treating patients with prostate cancer

Conditions: Prostate Cancer

Summary: rationale: androgens can stimulate the growth of prostate cancer cells. drugs such as flutamide and buserelin may stop the adrenal glands from producing androgens. ogx-011 may help flutamide and buserelin kill more tumor cells by making tumor cells more sensitive to the drugs. giving flutamide and buserelin with ogx-011 before surgery may shrink the tumor so it can be removed during surgery. purpose: phase i trial to study the effectiveness of combining hormone therapy with ogx-011 before radical prostatectomy in treating patients who have prostate cancer.

objectives: * determine the maximum tolerated dose and recommended phase ii dose of ogx-011 (clusterin antisense oligonucleotide) when administered with neoadjuvant hormonal therapy before radical prostatectomy in patients with adenocarcinoma of the prostate. * determine the toxicity of this regimen in these patients. * determine the pharmacokinetics of ogx-011 when this regimen is administered in these patients.. * assess the effects of this regimen on pathologic complete response rates in these patients. * correlate plasma and/or prostate concentrations of ogx-011 with patient response or toxicity measures. outline: this is a dose-escalation study of ogx-011. patients receive ogx-011 iv over 2 hours on days 1, 3, 5, 8, 15, 22, and 29; oral flutamide three times daily for 4 weeks; and buserelin subcutaneously on day 1. cohorts of 3-6 patients (except for 1 patient at starting dose) receive escalating doses of ogx-011 until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. the recommended phase ii dose is the dose preceding the mtd. patients undergo radical prostatectomy and bilateral pelvic lymphadenectomy 1 week after the last dose of neoadjuvant therapy. patients are followed at 7 days after surgery and then at 3 months. projected accrual: approximately 25-33 patients will be accrued for this study.

Eligibility criteria:
disease characteristics: * histologically confirmed adenocarcinoma of the prostate * high-risk, localized disease that is previously untreated * minimum of 2 positive biopsies * meets at least 1 of the following criteria: * stage t3 * serum psa greater than 10 ng/ml * gleason score 7-10 * gleason score 6 and at least 3 positive biopsies * potential candidate for radical prostatectomy patient characteristics: age * over 18 performance status * ecog 0-1 life expectancy * not specified hematopoietic * wbc at least 3,000/mm\^3 * platelet count at least 100,000/mm\^3 * hemoglobin at least 10.0 g/dl hepatic * bilirubin normal * ast and alt normal * ptt normal * inr normal renal * creatinine normal cardiovascular * no significant cardiac dysfunction other * fertile patients must use effective contraception * no known hypersensitivity to oligonucleotides, luteinizing hormone-releasing hormone analogs, or anti-androgens * no evidence of active uncontrolled infection * no other malignancy within the past 5 years except adequately treated nonmelanoma skin cancer * no other serious illness, psychiatric disorder, or medical condition that would preclude study compliance * no history of a significant neurological disorder that would preclude informed consent * no geographical condition that would preclude study compliance prior concurrent therapy: biologic therapy * not specified chemotherapy * no prior chemotherapy for prostate cancer endocrine therapy * no prior hormonal therapy for prostate cancer radiotherapy * no prior radiotherapy for prostate cancer * no concurrent radiotherapy surgery * not specified other * no concurrent heparin or warfarin anticoagulation * no other concurrent investigational therapy * no other concurrent cytotoxic therapy

Keywords: adenocarcinoma of the prostate stage iii prostate cancer stage ii prostate cancer